Pilot Evaluation of S-(3-[18F]Fluoropropyl)-d-Homocysteine and O-(2-[18F]Fluoroethyl)-d-Tyrosine as Bacteria-Specific Radiotracers for PET Imaging of Infection

Betts, Helen M; Luckett, Jeni C; Hill, Philip J

Abstract

Purpose
There is currently no ideal radiotracer for imaging bacterial infections. Radiolabelled D-amino acids are promising candidates because they are actively incorporated into the peptidoglycan of the bacterial cell wall, a structural feature which is absent in human cells. This work describes fluorine-18 labelled analogues of D-tyrosine and D-methionine, O-(2-[18F]fluoroethyl)-D-tyrosine (D-[18F]FET) and S-(3-[18F]fluoropropyl)-D-homocysteine (D-[18F]FPHCys), and their pilot evaluation studies as potential radiotracers for imaging bacterial infection.

Procedures
D-[18F]FET and D-[18F]FPHCys were prepared in classical fluorination-deprotection reactions, and their uptake in Staphylococcus aureus and Pseudomonas aeruginosa was evaluated over 2 h. Heat killed bacteria were used as controls. A clinically-relevant foreign body model of S. aureus infection was established in Balb/c mice, as well as a sterile foreign body to mimic inflammation. The ex vivo biodistribution of D-[18F]FPHCys in the infected and inflamed mice was evaluated after 1 h, by dissection and gamma counting. The uptake was compared to that of [18F]FDG.

Results
In vitro uptake of both D-[18F]FET and D-[18F]FPHCys was specific to live bacteria. Uptake was higher in S. aureus than in P. aeruginosa for both radiotracers, and of the two, higher for D-[18F]FPHCys than D-[18F]FET. Blocking experiments with non-radioactive D-[19F]FPHCys confirmed specificity of uptake. In vivo, D-[18F]FPHCys had greater accumulation in S. aureus infection compared with sterile inflammation, which was statistically significant. As anticipated, [18F]FDG showed no significant difference in uptake between infection and inflammation.

Conclusions
D-[18F]FPHCys uptake was higher in infected tissues than inflammation, and represents a fluorine-18 labelled D-AA with potential to detect a S. aureus reference strain (Xen29) in vivo. Additional studies are needed to evaluate uptake of this radiotracer in clinical isolates.

• Journal Article Type: Article
• Acceptance Date: Jun 14, 2024
• Online Publication Date: Jun 28, 2024
• Publication Date: 2024
• Deposit Date: Jul 4, 2024
• Publicly Available Date: Jul 4, 2024
• Journal: Molecular Imaging and Biology
• Print ISSN: 1536-1632
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1007/s11307-024-01929-7
• Public URL: https://nottingham-repository.worktribe.com/output/36579526
• Publisher URL: https://link.springer.com/article/10.1007/s11307-024-01929-7